Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure

Zaher S. Azzam, Vidas Dumasius, Fernando J. Saldias, Yochai Adir, Jacob I. Sznajder, Phillip Factor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Background - Acute elevation of left atrial pressure (LAP) increases extravascular water and impairs active Na+ transport in rat lungs. We have reported that overexpression of Na,K-ATPase subunit genes in the alveolar epithelium increases alveolar fluid clearance (AFC) in normal and injured rat lungs with normal LAP. We reasoned that adenovirus-mediated transfer of an Na,K-ATPase β-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP. Methods and Results - Normal rats were infected with 4 × 109 plaque-forming units of E1a-/E3- recombinant adenoviruses that contained a cytomegalovirus promoter coupled to a rat Na,K-ATPase β1-subunit cDNA (adβ1) or no cDNA (adNull) 7 days before study. Na,K-ATPase α1- and β1-subunit abundance in basolateral cell membranes isolated from the peripheral lung was significantly increased in adβ1-infected lungs compared with sham and adNull-infected controls. In all groups, elevation of LAP reduced membrane-bound Na,K-ATPase abundance; however, abundance in adβ1-infected lungs remained greater than in controls. AFC, measured with a fluid-filled isolated lung preparation in the presence of elevated LAP (15 cmH2O), in Na,K-ATPase β1subunit-overexpressing lungs was up to 100% greater than in controls and was not different from rats studied at normal LAP (0 cmH2O). Conclusions - These data suggest that alveolar overexpression of an Na,K-ATPase β1-subunit can counteract downregulation of membrane-bound solute transporters owing to elevated pulmonary vascular pressures and can restore active Na+ transport and AFC in this rat model of acute hydrostatic pulmonary edema.

Original languageEnglish (US)
Pages (from-to)497-501
Number of pages5
JournalCirculation
Volume105
Issue number4
DOIs
StatePublished - Jan 29 2002

Keywords

  • Edema
  • Epithelium
  • Genes
  • Heart failure
  • Viruses

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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